Multi-Modal Signals for Analyzing Pain Responses to Thermal and Electrical Stimuli
April 5th, 2019
This article focuses on the experimental elicitation of pain through heat (thermal) and electrical stimulation while recording physiological, visual, and paralinguistic responses. It aims at collecting valid multimodal data for analyzing pain based on its intensity, quality, and duration.
The data acquired with the presented method may shed light on how to recognize pain intensities, independently of the underlying pain model. It may also help to assess the pain duration. The main advantage of this technique is its multimodality in terms of signal recording and pain stimulation.
It significantly broadens the scope of pain research. This technique can be applied to monitor for pain presence in pathology treatment for more efficient pain management. The execution of he protocol requires many complex manual actions, such as electrode application, which are faster and easier to learn through visual demonstration.
Demonstrating the procedure will be Sandra Gebhardt, a student from my laboratory who is trained as an experimenter for this study. To prepare for the procedure, welcome the arriving subject and lead her to the calibration room. Inform her in detail about the calibration procedure and the following pain stimulation.
Next, conduct the pain stimulation in a camera-monitored, temperature-controlled and low-noise experimental room next to the calibration monitoring room. Use appropriate recording computers, software, and recording devices for capturing physiological data, audio, videos, and thermal and electrical stimulator outputs during the experiment. Enter the values of the phasic electrical and heat pain intensities and the tonic electrical and heat intensities calculated based on the performed calibration in the thermal and electrical stimulator.
Set the baseline temperature to 32 degrees Celsius and the temperature rate to 8 degrees Celsius per second, then save all settings. Subsequently, prepare the pain elicitation script, as shown here. Set the number of each phasic stimulus intensity to 30 and the number of each tonic stimulus intensity to one.
Then, set the duration of each phasic stimulus to five seconds and the duration of each tonic stimulus to 60 seconds. Randomize the order of all stimuli and the pauses between the phasic stimuli to eight to 12 seconds. After that, set the pauses after the tonic stimuli to 300 seconds.
To begin pain stimulation, ask the subject to lie down comfortably on the examination couch. Clean all skin areas where the electrodes will be attached with alcohol solution. Remove any dead skin cells on the surface of the left cheek, behind the left ear, above the left eyebrow, and on the forehead with abrasive gel.
Then, re-clean these areas with an alcohol solution. For the measurement of the skin conductance level, attach two pre-gelled nonpolorizable silver, silver chloride electrodes to the underside of the distal phalanx of the right index and middle finger with Velcro straps. To record ECG, use three pre-gelled adhesive silver, silver chloride snap electrodes with circular contact areas.
Place the cathode electrode on the chest, approximately six centimeters below the right collarbone and the anode electrode on the left 9th and 10th rib. Attach the reference electrode to the right side waist next to the pelvic bone. To record EMG of of musculus trapezius, also use three pre-gelled adhesive silver, silver chloride snap electrodes with circular contact areas.
Place the cathode and anode electrodes side by side on the trapezius muscle at the left side of the neck. Then, place the reference electrode below, on the left collarbone. Use six reusable shielded silver, silver chloride electrodes to measure the EMGs of musculus corrugator supercilii and musculus zygomaticus major.
Attach one side of the double-sided adhesive collars to the electrodes. Subsequently, fill the cavities of the electrodes with electrolyte gel. Remove the paper backings on the other side of the double-sided adhesive collars.
For musculus corrugator supercilii, place the anode electrode directly above the left eyebrow, next to the glabella line. Then, place the cathode electrode one centimeter lateral to the anode electrode. Attach the reference electrode to the middle of the frontal bone, just below the hairline.
For musculus zygomaticus major, draw an imaginary line from the left oral commissure to the left ear lobe. Place the anode electrode slightly below the middle of the line and the cathode electrode one centimeter medial next to it. Attach the reference electrode to the left mastoid.
Then, connect all the electrodes to the corresponding inputs of the biosignal recording device. Perform a visual check, using the biosignal recording software to make sure all physiological signals are of good, excellent quality. Next, place the silver, silver chloride anode electrode on the upper side of the intermediate phalanx of the left index finger and the cathode electrode on the upper side of the proximal phalanx of the left middle finger.
Connect the electrodes to the electrical stimulator. Apply the thermode to the upper side of the subject's left forearm, about 30 millimeters proximal to the wrist, with a Velcro strap. Start all the cameras.
Ensure that the participant is perfectly visible in the camera. Then, start all the recording devices, complying with the requirements for data synchronization. Run the pain elicitation script.
Carefully monitor the subject and the progress of the pain stimulation part. After the ending of the pain elicitation script, stop all the recording devices. Check if the participant is all right and detach all the electrodes and the thermode.
Next, wrap a hygienic, non-woven towel around a cold gel pack. Ask the participant to apply it on the skin area where the thermode was placed for at least five minutes. Then apply ointment to the skin area where the thermode was placed.
Afterward, thank the participant and say goodbye. Dispose of all the disposable electrodes. Clean all the reusable electrodes, and the examination couch.
Shown here are the images of the subject before, during, and after an intense pain stimulus. All the recorded signals are non-filtered and synchronized in time. For clarity, only representative screenshots of the video signals are shown.
While attempting this procedure, it's important to ensure all signals are optimized before starting the pain stimulation. Also ensure that all the recording devices are on before running the pain elicitation script. Following this procedure, other methods, like implementing a near infrared night vision camera, or recording for biosignals can be performed in order to recognize pain more efficiently in a nightly environment.
This technique allows for recognizing pain objectively without a need to communicate with the patient. It may be helpful to distinguish different pain properties and provide insight to the underlying source of pain. Pain stimulators can cause serious injuries if not operated by trained personnel.
Always follow the ethical and safety restrictions regarding stimulus intensity cutoffs to ensure the participants'safety.
Overview
This article focuses on the experimental elicitation of pain through heat and electrical stimulation while recording physiological, visual, and paralinguistic responses. It aims at collecting valid multimodal data for analyzing pain based on its intensity, quality, and duration.
Key Study Components
Area of Science
- Neuroscience
- Pain Research
- Physiological Measurement
Background
- The study explores pain recognition through various stimuli.
- It emphasizes the importance of multimodal data collection.
- Understanding pain intensity and duration is crucial for effective pain management.
- The technique broadens the scope of pain research.
Purpose of Study
- To analyze pain based on its intensity, quality, and duration.
- To develop a method for recognizing pain intensities independently of the underlying pain model.
- To assess the duration of pain through a systematic approach.
Methods Used
- Application of thermal and electrical stimulation to elicit pain.
- Recording physiological data, audio, video, and stimulator outputs.
- Calibration of equipment and preparation of subjects for pain elicitation.
- Monitoring and documenting the pain stimulation process.
Main Results
- The method allows for effective monitoring of pain presence.
- Physiological signals recorded are of high quality and synchronized.
- The protocol demonstrates the feasibility of multimodal pain assessment.
- Visual demonstrations enhance the learning of complex manual actions.
Conclusions
- The technique significantly contributes to pain research methodologies.
- It provides a comprehensive framework for pain management in clinical settings.
- Future studies can build on this method for further insights into pain mechanisms.
Frequently Asked Questions
Executive Industry Relevance
Objective pain assessment using multimodal physiological, audio, and video signals addresses a critical gap in translational research, especially for populations unable to communicate pain verbally. This approach enhances predictive confidence in pain response models and supports mechanistic de-risking at early discovery and preclinical stages. The resulting datasets and analytic frameworks enable more robust target validation and portfolio triage for pain-related therapeutics.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables objective interrogation of pain pathways using quantifiable multimodal signals.
- Supports functional target validation by correlating physiological and behavioral pain markers.
- Improves predictive confidence in pain model selection and mechanistic de-risking.
Screening & Assay Development
- Facilitates development of standardized, reproducible pain response assays using synchronized physiological and behavioral data.
- Provides quantitative outputs for benchmarking compound effects on pain intensity and duration.
- Enables scalable screening platforms for evaluating analgesic candidates in disease-relevant systems.
Translational & Preclinical Research
- Aligns preclinical pain models with human-relevant multimodal biomarkers for translational continuity.
- Supports risk-adjusted advancement decisions by integrating objective pain metrics into preclinical workflows.
- Enhances mechanistic understanding of pain responses across modalities and durations.
Pipeline & Workflow Integration
This multimodal pain assessment method integrates into the discovery-to-preclinical continuum, providing objective endpoints for hypothesis testing and model validation.
- Discovery Biology: Enables hypothesis-driven analysis of pain mechanisms using synchronized physiological and behavioral data.
- Screening: Delivers reproducible, quantitative pain response metrics for compound evaluation.
- Analytics: Supports statistical comparison of pain intensities, durations, and modalities across experimental conditions.
- Translational Research: Bridges preclinical and clinical pain assessment through objective, multimodal biomarkers.
- Enterprise Reuse: Establishes a reusable database and analytic framework for future pain research and assay development.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in pain research.
- Operational Value: Standardizes pain assessment protocols and improves reproducibility across studies.
- Strategic Value: Informs go/no-go decisions and enhances capital efficiency in analgesic development.
- Portfolio Impact: Enables risk-adjusted prioritization of pain-related therapeutic candidates.
Implementation Considerations
- Requires expertise in physiological signal acquisition and multimodal data synchronization.
- Demands specialized instrumentation for ECG, EMG, SCL, audio, and video capture.
- Necessitates rigorous cross-team standardization for protocol execution and data quality.
- Adaptation to additional pain modalities (e.g., pressure, chemical, cold) may require protocol modifications.
- Strict adherence to ethical and safety guidelines is essential to prevent participant harm.
